Module 9 2024

03/09/2024

Drug Development and Model Building Learning and confirming

Continuum of learn/confirm/predict at each decision point

M&S

M&S

M&S

M&S

M&S

Preclinical

Phase 1

Phase 3

Phase 4

Registration Labelling

Phase 2b

Phase 2a

FIH

POC Confirmatory

Results relative to competitors, regional differences, therapeutic index

Therapeutic Index

Efficacy

Toleration

Efficacy and safety

Toxicology

Human PK & PD

Dose/exposure-response

Covariate effects

PK-PD

Dose adjustments

Confidence in drug and disease

Uncertainty

M&S: Modelling and simulation; FIH: First-in-human; POC: Proof of concept; PK: Pharmacokinetics; PD: Pharmacodynamics

The Organisation for Professionals in Regulatory Affairs

Adapted from Lalonde RL et al. (2007) Clin.Pharmacol.Ther. 82:21-32

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Clinical Development

• Constantly seeking ways to improve the efficiency of clinical development of IMPs • Adaptive Trial Designs of Phase 1-2 studies

• Initial safety/tolerability, proof-of-concept (POC), dose finding

• Where feasible, investigate as many PD parameters as possible

Continually assessing the uncertainty

•

• Ability to modify depending upon the outcome of the assessment of uncertainty • Modelling and simulation

Based upon PK and PD results

•

• Informs on the IMP throughout clinical development to progress to the next phase

• Used to optimise the dose and dosing regimen

Assists to design more efficient POC

•

The Organisation for Professionals in Regulatory Affairs

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